BrdU does not induce hepatocellular damage in experimental Wistar rats.

Bromodeoxyuridine (BrdU) is used in studies related to cell proliferation and neurogenesis. The multiple intraperitoneal injections of this molecule could favor liver function profile changes. In this study, we evaluate the systemic and hepatocellular impact of BrdU in male adult Wistar rats in 30 %-partial hepatectomy (PHx) model. The rats received BrdU 50 mg/Kg by intraperitoneal injection at 0.5, 1, 2, 3, 6, 9 and 16 days after 30 %-PH. The rats were distributed into four groups as follows, control, sham, PHx/BrdU(-) and PHx/BrdU(+). On day 16, we evaluated hepatocellular nuclei and analyzed histopathological features by haematoxylin-eosin stain and apoptotic profile was qualified by caspase-3 presence. The systemic effect was evaluated by liver markers such as alanine transferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, total proteins and serum albumin content. The statistical analysis consisted of a student t-test and one-way ANOVA. BrdU did not induce apoptosis or hepatocellular damage in male rats. Multiple administrations of BrdU in male rats did not induce significant decrease body weight, but increased serum ALT and LDH levels were found. Our results show that the BrdU does not produce hepatocellular damage.

Altered liver function test after Covid-19 vaccines: A retrospective control group study.

BACKGROUND AND PURPOSE: Liver injury after Covid-19 vaccine has been described, although the incidence was not well established. We aimed to compare cumulative incidence of new onset liver test alteration after Covid-19 vaccination, and to compare with an historical control of influenza vaccination. METHODS: We conducted a retrospective cohort study which included adults who received at least one dose of Covid-19 vaccine from January 1 to May 30, 2021 and a control group who received a single dose of influenza vaccine during 2019, in a tertiary medical center from Argentina. RESULTS: We included 29 798 patients in Covid-19 vaccine group and 24 605 in influenza vaccine group. Liver function tests were performed in 7833 (26.9%) in Covid-19 vaccine group and 8459 (34.37%) in influenza vaccine group. Cumulative incidence at 90 days of new onset liver enzyme test alteration was 4.7 per 1000 (95% 4.0-5.5) for Covid-19 group, and 5.1 per 1000 (95% 4.3-6.1) for the influenza vaccine group (p value = 0.489). Two patients in the Covid-19 vaccine group developed immune mediated liver injury. CONCLUSIONS: We found no difference in liver test alteration between groups. These findings support the safety of Covid-19 vaccines. While we have identified two cases that are consistent with immune mediated liver injury following COVID-19 vaccination, we believe that the available data is insufficient to attribute them solely to the vaccination.

Identification of Predictors of Non-alcoholic Steatohepatitis and Its Severity in Individuals Undergoing Bariatric Surgery.

BACKGROUND: As obesity reached epidemic proportions, non-alcoholic fatty liver disease (NAFLD) also had a worrisome parallel increase. The non-invasive differentiation of non-alcoholic steatohepatitis (NASH) from uncomplicated NAFLD remains an important challenge in current clinical practice. OBJECTIVE: To identify predictors of the occurrence and severity of NAFLD and NASH. METHODS: This is an analytical cross-sectional study which included individuals undergoing bariatric surgery. Participants were histologically classified according to the presence NASH and severity of NAFLD. Demographic, clinical, anthropometric, and biochemical aspects were analyzed and compared. RESULTS: Out of 171 individuals, 87.7% were female and the mean age was 38.4±9.3 years. The average BMI was 38±3.0 kg/m2. NAFLD was histologically confirmed in 74.9%; the commonest histopathological abnormalities were macrovesicular steatosis (74.9%) and ballooning (40.4%). Simple steatosis occurred in 30.4%, 44.4% presented with NASH, and 31% had severe NAFLD. NASH associated with higher levels of ALT (0.03), ALP (0.02), and glucose (0.02). Cutoff values were, respectively, 23 U/L, 67 U/L, and 81 mg/dL. Their concomitant use provided an 83.1% specificity for NASH. Severe NAFLD associated with diabetes (p=0.02), higher BMI (p=0.01), AST (p=0.04), ALT (p<0.01), ALP (p=0.01), glucose (p=0.02), and ferritin (p<0.01). BMI over 39.3 kg/m2 and ferritin over 178 ng/mL concomitantly provided a 70.5% accuracy for severe NAFLD. CONCLUSIONS: NASH and severe NAFLD associated with higher levels of ALT, ALP, and glucose. Severe NAFLD associated with higher BMI and higher ferritin levels in this group. The concomitant evaluation of these laboratory tests could help ruling out NASH and safely screening severe NAFLD.

Fibrotic NASH in Individuals with Obesity: a Cross-sectional Analysis of the Prevalence of this Significant Milestone of Disease Progression and Accuracy of a Non-invasive Marker for its Screening.

BACKGROUND: Fibrotic non-alcoholic steatohepatitis (NASH), i.e., the concomitant presence of active inflammation and fibrosis, represents a milestone in the natural history of NAFLD and a critical time point in its progression. The purpose of this study was to analyze the diagnostic accuracy of the non-invasive Fibrotic NASH Index (FNI) in individuals with obesity undergoing bariatric surgery. METHODS: This is a cross-sectional study, enrolling individuals who underwent bariatric surgery with liver biopsy at a tertiary university hospital. FNI was calculated, and a cutoff value was determined. Its diagnostic accuracy was then calculated through comparison with the gold standard test for this analysis (histopathological examination). RESULTS: Of 128 participants, 83.6% were female, and the average age was 39.8 ± 8.7 years. The mean BMI was 38.7 ± 5.7 kg/m2. NAFLD was histologically confirmed in 76.6%, of which 81.6% had NASH. Histologically confirmed fibrotic NASH was observed in 22.7% of the general study population, 29.6% of individuals with NAFLD, and 36.3% of those with NASH. The mean FNI was 0.18 ± 0.19. An optimal cutoff point of 0.21 was determined, with an overall accuracy of 90.1%, an 82.8% sensitivity, a 90.8% specificity, a 72.6% positive predictive value, and a 94.7% negative predictive value. CONCLUSIONS: FNI provided adequate accuracy in detecting and ruling out fibrotic NASH. Considering the importance of fibrotic NASH within the natural history of NAFLD progression and the fact that this marker uses simple variables, it may be of great importance in high-risk populations, and its external validation and use should be encouraged.

Alteraciones en el perfil hepático y otros marcadores de pacientes asintomáticos que acuden a exámenes de rutina en un área urbana de Lima, Perú

Introducción: las enzimas y marcadores del perfil hepático permiten evaluar la funcionalidad y condición del hígado. Sus elevaciones pueden ser silentes y con cierta prevalencia en muchos adultos. Objetivo: determinar las principales alteraciones en el hepatograma en pacientes que acuden a consulta médica de rutina. Metodología: estudio descriptivo, prospectivo y transversal realizado a partir de resultados de laboratorio de historias clínicas de 364 pacientes de todas las edades y ambos sexos pertenecientes a un policlínico del distrito de Villa el Salvador, Perú desde enero de 2021 a julio de 2022. Las variables fueron: edad, sexo, valores de transaminasa glutámico pirúvica (TGP), transaminasa glutámico oxalacética (TGO), bilirrubina directa, indirecta y total, albúmina, globulinas y fosfatasa alcalina (FA). Resultados: en el promedio total de la muestra, la TGP fue alta (51,05 U/L), así como la bilirrubina total (1,50 mg/dL) y la FA (135,84 U/L). La TGP fue alta en hombres (54,92 U/L) y mujeres (48,86 U/L). La TGO fue normal en mujeres y alta en hombres (48,24 U/L). La bilirrubina indirecta fue alta en hombres (1,33 mg/dL). La FA fue más alta en ambos sexos (143,28 U/L en hombres y 126,38 en mujeres). Según grupo etario, los valores de TGO fueron más altos en el grupo de edad igual o mayor a 40 años (49,99 U/L). Los valores de TGP fueron elevados en ambos sexos (55,96 U/L en hombres y 50,90 U/L en mujeres), así como en la bilirrubina total, la que fue más alta en el grupo de edad igual o mayor a 40 años (2,03 mg/dL). La bilirrubina indirecta, albúmina y FA fueron normales en el grupo de edad igual o menor de 39 años, pero fueron elevadas en el grupo de edad igual o mayor a 40 años (1,13 mg/dL, 5,77 gr/dL y 147,95 U/L, respectivamente). Conclusiones: existen alteraciones en el perfil hepático en pacientes asintomáticos en la muestra estudiada. A pesar de no ser elevaciones significativamente grandes, se recomienda identificar y tratar las posibles causas que pudieran desencadenar dichas elevaciones, así como la realización de más estudios similares a nivel nacional para caracterizar el perfil hepático de nuestra población.

Introduction: The enzymes and markers of the liver profile allow us to evaluate the functionality and condition of the liver. Their elevations may be silent and have a certain prevalence in many adults. Objective: To determine the main alterations in the hepatogram in patients who attend routine medical consultation. Methodology: Descriptive, prospective and cross-sectional study carried out based on laboratory results from medical records of 364 female and male patients of all ages attending a polyclinic in the district of Villa El Salvador, Peru from January 2021 to July 2022. The variables were: age, sex, values ​​of alanine aminotransferase (ALT), aspartate transaminase (AST), direct, indirect and total bilirubin, albumin, globulins and alkaline phosphatase (ALP). Results: In the total average of the sample, ALT was high (51.05 U/L), as well as total bilirubin (1.50 mg/dL) and ALP (135.84 U/L). ALT was high in men (54.92 U/L) and women (48.86 U/L) while AST was normal in women and high in men (48.24 U/L). Indirect bilirubin was high in men (1.33 mg/dL) and ALP was higher in both sexes (143.28 U/L in men and 126.38 in women). According to age group, AST values ​​were highest in the age group equal to or greater than 40 years (49.99 U/L). ALT values ​​were high in both sexes (55.96 U/L in men and 50.90 U/L in women), as well as total bilirubin, which was highest in the age group equal to or greater than 40 years (2.03 mg/dL). Indirect bilirubin, albumin and ALP were normal in the age group equal to or less than 39 years, but were elevated in the age group equal to or greater than 40 years (1.13 mg/dL, 5.77 gr/dL and 147.95 U/L, respectively). Conclusions: There are alterations in the liver profile of asymptomatic patients in the sample studied. Although they are not significantly large elevations, it is recommended to identify and treat the possible causes that could trigger these elevations, as well as carrying out more similar studies at a national level to characterize the liver profile of our population.

NI-NASH-DS e FIB-4 para avaliação de diferentes aspectos da doença hepática gordurosa não-alcoólica em indivíduos com obesidade: estudo transversal / Diagnostic accuracy of the non-invasive markers nfls, ni-nash-ds, and fib-4 for assessment of different aspects of non-alcoholic fatty liver disease in individuals with obesity: cross-sectional study

ABSTRACT Background: Non-invasive markers have been developed to assess the presence and severity of liver abnormalities related to non-alcoholic fatty liver disease (NAFLD). Objective: To analyze the diagnostic accuracy of non-invasive NAFLD markers (NAFLD liver fat score [NLFS], non-invasive non-alcoholic steatohepatitis detection score [NI-NASH-DS] and fibrosis score based on four variables [FIB-4]) in individuals with obesity undergoing bariatric surgery. Methods: A descriptive retrospective cross-sectional study was carried out enrolling 91 individuals who underwent bariatric surgery at a tertiary-level public university hospital. Non-invasive NAFLD markers were calculated using laboratory tests, clinical and anthropometric variables and diagnostic accuracy tests were calculated comparing them in relation to the gold-standard test for this analysis (histopathological evaluation). Results: A total of 85.7% of the participants were female and mean age was 39.1±9.8 years. The average body mass index was 38.4±3.6 kg/m2. At histopathological examination, 84 (92.3%) patients presented with steatosis, 82 (90.1%) with some type of fibrosis; 21 (23.1%) patients were diagnosed with NASH according to the NAFLD activity score criteria. The overall accuracy of NLFS score was 58.2% for general hepatic steatosis and 61.5% for moderate to severe steatosis. The overall accuracy of FIB-4 was 95.4% for advanced fibrosis. NI-NASH-DS had a 74.7% overall accuracy for NASH. Conclusion: In a population of individuals with obesity, the FIB-4 score had high overall accuracy in assessing the presence of advanced liver fibrosis, whereas the NFLS and NI-NASH-DS had moderate accuracies for the assessment of steatosis and NASH, respectively.

RESUMO Contexto: Marcadores não-invasivos foram desenvolvidos para avaliar a presença e a gravidade de anormalidades hepáticas relacionadas à doença hepática gordurosa não-alcoólica (DHGNA). Objetivo: Analisar a acurácia diagnóstica de marcadores não-invasivos de DHGNA (escore de gordura hepática da DHGNA [NLFS], escore não-invasivo de detecção de esteato-hepatite não-alcoólica [NI-NASH-DS] e escore de fibrose de 4 variáveis [FIB-4]) em indivíduos obesos submetidos à cirurgia bariátrica. Métodos: Foi realizado um estudo descritivo retrospectivo transversal com 91 indivíduos submetidos à cirurgia bariátrica em um hospital universitário público de nível terciário. Marcadores não-invasivos de DHGNA foram calculados por meio de exames laboratoriais, variáveis clínicas e antropométricas; testes de acurácia diagnóstica foram calculados comparando-os em relação ao exame padrão-ouro para essa análise (avaliação histopatológica). Resultados: Um total de 85,7% dos participantes eram do sexo feminino e a média de idade foi de 39,1±9,8 anos. O índice de massa corporal médio foi de 38,4±3,6 kg/m2. Ao exame histopatológico, 84 (92,3%) pacientes apresentavam esteatose, 82 (90,1%) com algum grau de fibrose; 21 (23,1%) pacientes foram diagnosticados com esteato-hepatite não-alcoólica (EHNA) de acordo com os critérios do escore de atividade da DHGNA. A acurácia global do escore NLFS foi de 58,2% para esteatose hepática e 61,5% para esteatose moderada a grave. A acurácia global do FIB-4 foi de 95,4% para fibrose avançada. NI-NASH-DS apresentou uma acurácia global de 74,7% para EHNA. Conclusão: Em uma população de indivíduos com obesidade, o escore FIB-4 teve alta acurácia global para avaliar a presença de fibrose hepática avançada, enquanto o NFLS e o NI-NASH-DS tiveram acurácias moderadas para avaliar a esteatose e EHNA, respectivamente.

Protection of Liver Functions and Improvement of Kidney Functions by Twelve Weeks Consumption of Cuban Policosanol (Raydel®) with a Decrease of Glycated Hemoglobin and Blood Pressure from a Randomized, Placebo-Controlled, and Double-Blinded Study with Healthy and Middle-Aged Japanese Participants.

Policosanol consumption has been associated with treating blood pressure and dyslipidemia by increasing the level of high-density lipoproteins-cholesterol (HDL-C) and HDL functionality. Although policosanol supplementation also ameliorated liver function in animal models, it has not been reported in a human clinical study, particularly with a 20 mg doage of policosanol. In the current study, twelve-week consumption of Cuban policosanol (Raydel®) significantly enhanced the hepatic functions, showing remarkable decreases in hepatic enzymes, blood urea nitrogen, and glycated hemoglobin. From the human trial with Japanese participants, the policosanol group (n = 26, male 13/female 13) showed a remarkable decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from baseline up to 21% (p = 0.041) and 8.7% (p = 0.017), respectively. In contrast, the placebo group (n = 26, male 13/female 13) showed almost no change or slight elevation. The policosanol group showed a 16% decrease in γ-glutamyl transferase (γ-GTP) at week 12 from the baseline (p = 0.015), while the placebo group showed a 1.2% increase. The policosanol group exhibited significantly lower serum alkaline phosphatase (ALP) levels at week 8 (p = 0.012), week 12 (p = 0.012), and after 4-weeks (p = 0.006) compared to those of the placebo group. After 12 weeks of policosanol consumption, the ferric ion reduction ability and paraoxonase of serum were elevated by 37% (p < 0.001) and 29% (p = 0.004) higher than week 0, while placebo consumption showed no notable changes. Interestingly, glycated hemoglobin (HbA1c) in serum was lowered significantly in the policosanol group 4 weeks after consumption, which was approximately 2.1% (p = 0.004) lower than the placebo group. In addition, blood urea nitrogen (BUN) and uric acid levels were significantly lower in the policosanol group after 4 weeks: 14% lower (p = 0.002) and 4% lower (p = 0.048) than those of the placebo group, respectively. Repeated measures of ANOVA showed that the policosanol group had remarkable decreases in AST (p = 0.041), ALT (p = 0.008), γ-GTP (p = 0.016), ALP (p = 0.003), HbA1c (p = 0.010), BUN (p = 0.030), and SBP (p = 0.011) from the changes in the placebo group in point of time and group interaction. In conclusion, 12 weeks of 20 mg consumption of policosanol significantly enhanced hepatic protection by lowering the serum AST, ALT, ALP, and γ-GTP via a decrease in glycated hemoglobin, uric acid, and BUN with an elevation of serum antioxidant abilities. These results suggest that improvements in blood pressure by consumption of 20 mg of policosanol (Raydel®) were accompanied by protection of liver function and enhanced kidney function.

Application of Scores Assessing Histological Activity and Estimated Long-Term Risk Analysis of Hepatic Decompensation of Non-Alcoholic Fatty Liver Disease in Individuals Undergoing Bariatric Surgery.

BACKGROUND: Histological scores can estimate disease staging, allowing a standardization of the assessment of non-alcoholic fatty liver disease (NAFLD). The prediction of risk of NAFLD progression is relevant to allow the planning of interventions. OBJECTIVE: To analyze the application of the Iowa NAFLD decompensation risk score, the NAFLD activity score (NAS), and steatosis-activity-fibrosis score (SAF) and to assess correlations between these scores. METHODS: This is a retrospective cross-sectional study enrolling 76 individuals who underwent bariatric surgery at a tertiary university hospital. Liver biopsy was performed during procedures; histological scores were then assessed. The Iowa score was calculated using age, diabetes, and platelet count. RESULTS: 89.5% were female and mean age was 39.1 ± 9.6 years. Mean BMI was 38.2 ± 3.7 kg/m2. Steatosis (92.1%), hepatocellular ballooning (93.4%), lobular inflammation (93.4%), and fibrosis (97.4%) were the commonest histopathological findings. According to NAS, 22.4% had definite non-alcoholic steatohepatitis (NASH). According to SAF, 89.5% had moderate or severe NAFLD. The mean risks of NAFLD decompensation at 5, 10, and 12 years were 0.8%, 2.5%, and 2.9%, respectively. The group whose risk of decompensation was above 10% comprised 2.6% and 5.3% at 10 and 12 years, respectively. The severity assessed by SAF significantly associated with definite NASH diagnosis through NAS (p < 0.001). Iowa score did not correlate with both NAS/SAF scores. CONCLUSION: The Iowa score demonstrated that individuals with obesity present with a significant long-term risk of NAFLD-related events. There were high rates of moderate/severe forms of NAFLD assessed by NAS and SAF scores. There were no significant correlations between Iowa and NAS/SAF scores.

Gastrointestinal manifestations of COVID-19 in a Colombian population. A cross-sectional study

Introduction: gastrointestinal involvement in COVID-19 occurs in approximately 20% of patients and may include nausea, vomiting, abdominal pain, diarrhea or abnormal liver function tests. In our country, the characteristics of gastrointestinal involvement in COVID-19 patients have not been studied. Objectives: to determine the prevalence of gastrointestinal and liver involvement in patients with COVID-19 treated at two hospitals in Bogotá, Colombia. To determine the association between COVID-19 gastrointestinal involvement and length of hospital stay, severity and mortality. Design and methodology: a cross-sectional study carried out at two hospitals in a hospital subnetwork in Bogotá, Colombia from February 2020 to March 2021. Results: a total of 1,176 patients with a positive reverse transcription polymerase chain reaction (RT-PCR) were included. Gastrointestinal manifestations occurred in 50% (95%CI 47-52%), with the most frequent being diarrhea in 18.4%, odynophagia in 17.6%, anorexia in 14.7% and abdominal pain in 8.8%. An association was found between diarrhea during hospitalization and prolonged hospitalization (OR 1.93 95%CI 1.19-3.13), and between gastrointestinal bleeding on admission and death (OR 3.13, 95%CI 1.1-9.1), among others. Abnormal liver function tests occurred in 46% (95%CI 43-49%) and were more frequent in patients with severe disease and those who died. Conclusions: the prevalence of gastrointestinal manifestations in patients with COVID-19 was 50%. Diarrhea was associated with a longer hospital stay, and gastrointestinal bleeding was associated with respiratory failure and death. Forty-six percent of patients had abnormal liver function tests, with elevated transaminases being the most frequent. Elevated aspartate transaminase (AST) on admission was associated with greater mortality. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2729).

Relative enhancement index can be used to quantify liver function in cirrhotic patients that undergo gadoxetic acid-enhanced MRI.

OBJECTIVES: To evaluate MRI with gadoxetic acid to quantify liver function in cirrhotic patients using the relative enhancement index (REI) compared with Child-Pugh score (CPS), MELD score, and indocyanine green plasma disappearance rate (ICG-PDR) and to establish cutoffs for REI to stratify cirrhotic patients into good and poor liver function groups. METHODS: We prospectively evaluated 60 cirrhotic patients and calculated CPS, MELD score, ICG-PDR, and REI for each patient. Spearman's correlation coefficient was used to assess correlation between REI, CPS, MELD, and ICG-PDR. Good and poor liver function groups were created by k-means clustering algorithm using CPS, MELD, and ICG-PDR. ROC curve analysis was performed and optimal cutoff was identified for group differentiation. RESULTS: Good correlations were found between REI and other liver function biomarkers: REI and CPS (rho = - 0.816; p < 0.001); REI and MELD score (rho = - 0.755; p < 0.001); REI and ICG-PDR (rho = 0.745; p < 0.001)]. REI correlation was stronger for patients with Child-Pugh A (rho = 0.642, p = 0.002) and B (rho = 0.798, p < 0.001) than for those with Child-Pugh C (rho = 0.336, p = 0.148). REI is significantly lower in patients with poor liver function (p < 0.001). ROC curve showed an AUC 0.94 to discriminate patients with poor liver function (REI cutoff < 100; 100% sensitivity; 76% specificity). CONCLUSIONS: REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. REI can be easily calculated and can be used to estimate liver function in clinical practice in the routine evaluation of cirrhotic patients that undergo MR imaging with gadoxetic acid contrast. KEY POINTS: • REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. • REI can be easily calculated in the routine evaluation of cirrhotic patients that undergo gadoxetic acid-enhanced MRI. • The REI enables stratification of cirrhotic patients into good and poor liver function groups and can be used as additional information, together with morphological and focal liver lesion evaluation.

Níveis séricos de vitamina D e alterações hepáticas em pacientes com malária na região Amazônica / Serum levels of vitamin d and hepatic changes in patients with malaria in the Amazon region / Niveles séricos de vitamina d y alteraciones hepáticas en pacientes con malaria en la Amazonia

Vários estudos sugerem a importância da vitamina D ­ 25(OH)D ­ na evolução clínica dos pacientes com malária. Entretanto, a prevalência de deficiência de 25(OH)D na população amazônica é pouco conhecida, havendo também poucos estudos com pacientes diagnosticados com malária. Assim, o objetivo deste estudo foi avaliar os níveis séricos de 25(OH)D em pacientes com malária e sua relação com dados epidemiológicos, parasitológico e provas de função hepática. Para tanto, foi realizado um estudo transversal analítico com um grupo de pacientes com malária e um grupo controle no município de Itaituba (PA), Brasil, no período de janeiro de 2018 a outubro de 2019. Elaborou-se um protocolo para avaliação dos dados sociodemográficos, parasitológicos e laboratoriais, adotando-se o nível de significância de 5%. A prevalência de deficiência de 25(OH)D foi observada nos pacientes com malária (28,5%) e no grupo controle (24,6%), sem diferença estatística; porém, entre os residentes no garimpo, os níveis séricos foram estatisticamente menores nos pacientes com malária. Os níveis séricos de transaminase glutâmico-pirúvica (TGP) apresentaram correlação inversa com os de 25(OH)D. As provas de função hepática foram significativamente maiores no grupo com malária. Dessa forma, este estudo evidenciou a deficiência de 25(OH)D em Itaituba. Alterações hepáticas pela infecção plasmodial podem ter contribuído para a correlação inversa observada entre os níveis de TGP e 25(OH)D.

Several studies suggest the importance of vitamin D ­ 25(OH)D ­ in the clinical evolution of patients with malaria. However, the prevalence of 25(OH)D deficiency in the Amazonian population is little known, and studies with patients diagnosed with malaria are scarce. Thus the objective of this study is to evaluate the serum levels of 25(OH)D in patients with malaria and its relationship with epidemiological and parasitological data and liver function tests. To that end, an analytical cross-sectional study was carried out with a group of patients with malaria and a control group in the municipality of Itaituba (PA), Brazil, from January 2018 to October 2019. A protocol was elaborated for the evaluation of sociodemographic, parasitological, and laboratory data, adopting a significance level of 5%. Results: The prevalence of 25(OH)D deficiency was observed in patients with malaria (28.5%) and in the control group (24.6%), with no statistical difference; however, among residents in the mining, serum levels were statistically lower in patients with malaria. The glutamic-pyruvic transaminase (GPT) serum levels showed an inverse correlation with 25(OH)D levels. Liver function tests were significantly higher in the malaria group. Thus, this study evidenced 25(OH)D deficiency in Itaituba. Hepatic changes due to plasmodial infection may have contributed to the inverse correlation observed between GPT and 25(OH)D levels.

Diversos estudios sugieren la importancia de la vitamina D ­[25(OH)D]­ en la evolución clínica de pacientes con malaria. Sin embargo, la prevalencia de la deficiencia de 25(OH)D en la población amazónica es poco conocida y existen pocos estudios en pacientes con malaria. Ante esto, el objetivo de este estudio fue evaluar los niveles séricos de 25(OH)D en pacientes con malaria y su relación con datos epidemiológicos, parasitológicos y pruebas de función hepática. Para ello, se realizó un estudio transversal analítico en el grupo de pacientes con malaria y en un grupo control en el municipio de Itaituba (PA), Brasil, de enero de 2018 a octubre de 2019. Se elaboró un protocolo para la evaluación de datos sociodemográficos, parasitológicos y de laboratorio, adoptando un nivel de significancia del 5%. La prevalencia de deficiencia de 25(OH)D se observó en pacientes con malaria (28,5%) y en el grupo control (24,6%), sin diferencia estadística; sin embargo, entre los residentes en la minería, los niveles séricos fueron estadísticamente inferiores en pacientes con malaria. Los niveles séricos de transaminasa glutámico pirúvica (TGP) mostraron una correlación inversa con los niveles de 25(OH)D. Las pruebas de función hepática fueron significativamente más altas en el grupo de malaria. De esta manera, se evidenció deficiencia de 25(OH)D en la población de Itaituba. Los cambios hepáticos debido a la infección plasmodial pueden haber contribuido a la correlación inversa observada entre los niveles de TGP y 25(OH)D.

Impact and outcomes of liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension.

PURPOSE: Clinically significant portal hypertension (CSPH), although not a contraindication for liver resection in cirrhosis, is considered a determinant prognostic factor for post-surgical outcomes. This study aims to investigate the effects of CSPH on short and long-term results after hepatic resection for hepatocellular carcinoma (HCC). METHODS: Single-center retrospective analysis of 126 consecutive hepatic resections for HCC in Child-Pugh A patients, performed between 2008 and 2018. Patients were divided according to the presence of CSPH, defined as a hepatic venous pressure gradient ≥ 10 mmHg. To overcome selection bias, 42 patients with CSPH were matched through propensity score with 42 patients without CSPH. Intraoperative and post-operative outcomes, along with overall and disease-free survival, were compared between the matched groups. RESULTS: Liver decompensation was four-fold in the CSPH group (28.6% vs. 7.1%, p = 0.010), while rate of severe complications, including 90-days mortality, was not statistically different between patients with and without CSPH. Overall and recurrence-free survival was not inferior in patients with CSPH compared to non-CSPH group. CONCLUSIONS: The present study has demonstrated acceptable outcomes of liver resection for HCC in carefully selected Child-Pugh A cirrhotic patients, even in the presence of elevated portal pressure.

OBJETIVOS: La hipertensión portal clínicamente significativa (HPCS), si bien no representa una contraindicación para la resección hepática en la cirrosis, se considera un factor pronóstico determinante en los resultados posoperatorios. Este estudio se propone de estudiar los efectos de la HPCS en los resultados a corto y largo plazo tras la resección hepática por carcinoma hepatocelular (CHC). MÉTODOS: Análisis retrospectivo mono-céntrico de 126 resecciones hepáticas por CHC en pacientes Child-Pugh A, realizadas entre el 2008 y el 2018. Los pacientes se han dividido según la presencia de HPCS, definida como gradiente de presión venoso hepático ≥ 10 mmHg. Para controlar el sesgo de selección, 42 pacientes con HPCS se han apareado con puntaje de propensión con 42 pacientes sin HPCS. RESULTADOS: La tasa de descompensación hepática fue 4 veces superior en los pacientes con HPCS (28.6% vs. 7.1%, p = 0.010), mientras las complicaciones graves, incluyendo la mortalidad a 90 días, no se mostraron diferentes en los pacientes con y sin HPCS. La supervivencia global y libre de recidiva no fueron inferiores en los pacientes con HPCS comparados. CONCLUSIONES: El presente estudio ha demostrado resultados aceptables en la resección hepática en pacientes con cirrosis Child-Pugh A cuidadosamente seleccionados, también en presencia de hipertensión portal.

The Association between Mercury and Lead Exposure and Liver and Kidney Function in Pregnant Surinamese Women Enrolled in the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH) Environmental Epidemiologic Cohort Study.

Exposure to mercury (Hg) and lead (Pb) may have an effect on pregnant women. We assessed the effect of exposure to mercury and lead on liver and kidney functions in a subcohort of pregnant women who participated in the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH)­Meki Tamara, study. From 400 women aged 16−46 living in rural, urban, and interior regions of Suriname, we measured blood mercury and blood lead levels. Creatinine, urea, and cystatin C were measured to assess kidney function, and aspartate amino transferase (AST), alanine amino transferase (ALT), and gamma-glutamyl transferase (GGT) were measured to assess liver function. Education, region, and ethnicity showed significant differences for both blood mercury and lead levels, which all had p-values < 0.001. Creatinine and urea were elevated with higher mercury blood levels. Our findings also suggest a relationship between high mercury blood levels and potential harmful effects on liver and kidney function.

Drug-induced liver injury after covid-19 mRNA vaccine: case report

Case description: A 22-year-old female patient received the first dose of Pfizer-BioNTech vaccine (RNAm) against COVID-19; 6 days later, she presented abdominal pain located in the right hypochondrium and epigastrium, associated with emetic episodes. Re-consultation 21 days later due to the same symptoms; three days after the second dose of the vaccine was administered. Clinical findings: Pain on palpation in the right hypochondrium. Laboratories reported hepatocellular lesion and cholestasis, with negative amylase, hepatotropic virus and autoimmune hepatitis tests. Liver and biliary tract ultrasound and cholangioresonance were normal. Treatment and Results: Hyoscine and intravenous fluids as support therapy. She presented improvement in abdominal pain and progressive decrease of transaminases and bilirubin levels until normalization, and was discharged on the fifth day of hospitalization. A drug-associated hepatotoxicity (DILI) diagnosis was considered probable, in this case, secondary to vaccination against COVID-19. Clinical Relevance: The current SARS CoV-2 pandemic has spurred the development of new vaccines, the safety of which remains a concern. There is a likely causal relationship between vaccination and liver involvement in this clinical case, rather than simply a sporadic occurrence.

Descripción del caso: Paciente femenina de 22 años, quien recibió primera dosis de vacuna Pfizer-BioNTech (RNAm) contra COVID-19; presenta 6 días después, dolor abdominal localizado en hipocondrio derecho y epigastrio, asociado a episodios eméticos. Reconsulta a los 21 días por la misma sintomatología; tres días posteriores a la aplicación de la segunda dosis de la vacuna. Hallazgos clínicos: dolor a la palpación en hipocondrio derecho. Los laboratorios reportaron lesión hepatocelular y colestasis, con amilasa, estudios para virus hepatotrópos y hepatitis autoinmune negativos. La ecografía de hígado, vías biliares y colangioresonancia fueron normales. Tratamiento y Resultados: hioscina 20 mg vía oral cada 8 horas y líquidos endovenosos como terapia de soporte. Presentó mejoría del dolor abdominal y descenso progresivo de transaminasas y bilirrubinas, hasta su normalización y se dio egreso al quinto día de hospitalización. Se consideró probable diagnóstico de hepatotoxicidad asociada a medicamentos (DILI), en este caso, secundario a la vacunación contra COVID-19. Relevancia Clínica: La pandemia actual por el virus SARS CoV-2 ha impulsado el desarrollo de nuevas vacunas, cuya seguridad sigue siendo un motivo de preocupación. En este caso clínico, hay una probable relación causal entre la vacunación y el compromiso hepático, en lugar de una simple aparición esporádica.

Correlation between liver lipidosis, body condition score variation, and hepatic analytes in dairy cows.

Liver lipidosis is a metabolic disorder mostly observed in high yielding dairy cattle, especially during the transition period. The aim of this study was to determine the correlation between hepatic lipid infiltration, biochemical indicators of liver function, and body condition score (BCS) variation in dairy cows. Fifty-one multiparous Holstein cows raised in a confined system were evaluated. Liver biopsies and blood samples were collected, and BCS was measured on days 3 and 28 postpartum. Lipid infiltration was determined by histologic examination. The plasma activity of aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase and concentration of beta-hydroxybutyrate, non-esterified fatty acids, albumin, total bilirubin, and cholesterol were determined. BCS was measured using objective (camera) and subjective (visual) methods. Mild lipid infiltration was found in 3.92% of cows sampled on day 3 and 5.88% on day 28. Bilirubin was significantly higher on day 3 than on day 28 postpartum, and cholesterol was significantly higher on day 28 than on day 3 in all cows. There was no difference in biochemical analytes between cows with and without lipidosis. On day 3, mean subjective BCS was 3.10 and objective BCS was 3.16, while on day 28, these scores were 2.91 and 2.99, respectively. The calculated liver function index (LFI) was found to be a more sensitive indicator of liver function than the hepatic analytes evaluated. No correlation between BCS variation and lipid infiltration was found. Cholesterol and bilirubin levels showed the most remarkable changes during the early postpartum period. LFI is a potential indicator of postpartum liver function.

A lipidose hepática é um distúrbio metabólico principalmente observado nos bovinos de leite de alto rendimento, especialmente no período de transição. O objetivo deste estudo foi determinar a correlação entre infiltração lipídica hepática, indicadores bioquímicos de função hepática e variação da condição corporal em bovinos leiteiros. Foram avaliadas cinquenta e um vacas multíparas de raça Holandesa em confinamento. Coletaram-se biopsias de fígado e amostras de sangue, e a condição corporal (BCS) aferiu-se nos dias 3 e 28 pós-parto. A infiltração lipídica determinou-se mediante avaliação histológica. Mensuraram-se a atividade da aspartato aminotransferase, fosfatase alcalina e da gama-glutamil transferase, concentração de beta-hidroxibutirato, ácidos graxos não esterificados, albumina, bilirrubina total e colesterol. A BCS mediu-se utilizando método objetivo (câmera) e subjetivo (visualmente). Observou-se discreta infiltração lipídica em 3,92% dos bovinos amostrados no dia 3 e 5,88% no dia 28. Em todos os bovinos a bilirrubina foi significativamente mais alta no dia 3 do que no dia 28 e o colesterol foi superior no dia 28 do que no dia 3. Não houve diferença nos analitos bioquímicos dos bovinos com e sem lipidose. No dia 3, a média subjetiva da BCS foi 3,10 e a objetiva 3,16, enquanto no dia 28, obtiveram-se valores de 2,91, e 2,99 respectivamente. O índice calculado de função hepática mostrou ser um indicador mais sensível da função hepática do que os analitos avaliados individualmente. Não houve correlação entre a variação do BCS e infiltração lipídica.

Anticonvulsant Effect of Turmeric and Resveratrol in Lithium/Pilocarpine-Induced Status Epilepticus in Wistar Rats.

Epilepsy is a chronic neurological disorder that lacks a cure. The use of plant-derived antioxidant molecules such as those contained in turmeric powder and resveratrol may produce short-term anticonvulsant effects. A total of 42 three-month-old male Wistar rats were divided into six groups (n = 7 in each group): Vehicle (purified water), turmeric (150 and 300 mg/kg, respectively), and resveratrol (30 and 60 mg/kg, respectively), administered per os (p.o.) every 24 h for 35 days. Carbamazepine (300 mg/kg/5 days) was used as a pharmacological control for anticonvulsant activity. At the end of the treatment, status epilepticus was induced using the lithium-pilocarpine model [3 mEq/kg, intraperitoneally (i.p.) and 30 mg/kg subcutaneously (s.c.), respectively]. Seizures were evaluated using the Racine scale. The 300 mg/kg of turmeric and 60 mg/kg of resveratrol groups had an increased latency to the first generalized seizure. The groups treated with 150 and 300 mg/kg of turmeric and 60 mg/kg of resveratrol also had an increased latency to status epilepticus and a decreased number of generalized seizures compared to the vehicle group. The chronic administration of turmeric and resveratrol exerts anticonvulsant effects without producing kidney or liver damage. This suggests that both of these natural products of plant origin could work as adjuvants in the treatment of epilepsy.

Disfunção hepática em pacientes de unidade de terapia intensiva médica prevê desfecho desfavorável / Hepatic dysfunction in medical intensive careunit patients predicts poor outcome

ABSTRACT Background: A large number of patients admitted to the medical intensive care unit (MICU) have abnormal liver function tests (LFT). This includes patients with critical illness with or without preexisting liver disease and patients with acute primary liver injury. There are very few studies which have investigated the spectrum of liver disease, clinical profile and outcome in patients admitted to the MICU. Objective To evaluate the occurrence, etiology, clinical profile, laboratory profile and outcome of hepatic dysfunction in patients admitted to the MICU. To evaluate the utility of model for end-stage liver disease (MELD) score on admission as a predictor of adverse short term outcome in patients with hepatic dysfunction admitted in MICU. Methods: It was a prospective observational study, conducted from December 2017 to December 2018 in a tertiary care hospital. Two hundred and two patients admitted to the MICU with LFTs as per the inclusion criteria were analyzed and their short-term outcome at 7 days was studied in relation to various parameters. Results: LFT abnormalities were present in 202/1126 (17.9%) of the patients admitted to MICU. Critical illness associated liver dysfunction was found in 172 (85.2%) patients, chronic liver disease in 11 (5.4%) patients and acute viral hepatitis in 19 (9.4%) patients. Most common symptom was fever (68.3%) followed by vomiting (48.0%). Among LFT abnormalities, elevated transaminases, raised international normalized ratio and high MELD score on admission correlated with poor short-term outcome. Requirement for inotropes and mechanical ventilation correlated with poor short-term outcome. Mortality did not differ significantly between patients with chronic liver disease, patients with acute viral hepatitis and patients with critical illness associated hepatic dysfunction. Hepatic dysfunction in MICU was associated with poor outcome and a high short-term mortality of 56.4% (114/202). Conclusion: Liver function abnormality is common in patients who are admitted to the MICU and its presence is an indicator of poor short-term outcome.

RESUMO Contexto: Um grande número de pacientes internados na unidade de terapia intensiva (UTI) tem testes de função hepática anormais (TFH). Isso inclui pacientes com doença crítica com ou sem doença hepática pré-existente e pacientes com lesão hepática primária aguda. Há poucos estudos que têm investigado o espectro da doença hepática, perfil clínico e desfecho em pacientes admitidos em UTI. Objetivo Avaliar a ocorrência, etiologia, perfil clínico, perfil laboratorial e desfecho de disfunção hepática em pacientes internados na UTI médica. Avaliar a utilidade do modelo para doença hepática em estágio terminal (MELD). Escore na admissão como preditor de desfecho adverso a curto prazo em pacientes com disfunção hepática admitida em UTI. Métodos: Foi realizado um estudo observacional prospectivo, de dezembro de 2017 a dezembro de 2018 em um hospital de atenção terciária. Foram analisados 202 pacientes internados na UTI com TFH conforme os critérios de inclusão e seu desfecho a curto prazo de 7 dias foi estudado em relação a diversos parâmetros. Resultados: Anormalidades dos testes estiveram presentes em 202/1126 (17,9%) dos pacientes internados na UTI. Doença crítica associada à disfunção hepática foi encontrada em 172 (85,2%) pacientes, doença hepática crônica em 11 (5,4%) pacientes e hepatite viral aguda em 19 (9,4%) pacientes. O sintoma mais comum foi a febre (68,3%), seguido de vômito (48,0%) casos. Entre as anormalidades do TFH, transaminases elevadas, INR e escore MELD elevados na admissão correlacionaram-se com desfecho ruim de curto prazo. Exigência de inotrópicos e ventilação mecânica correlacionaram-se com desfecho de curto prazo ruim. A mortalidade não diferiu significativamente entre pacientes com doença hepática crônica, pacientes com hepatite viral aguda e pacientes com doença crítica associada à disfunção hepática. A disfunção hepática em UTI esteve associada a um desfecho ruim e à uma alta mortalidade a curto prazo de 114/202 (56,4%). Conclusão: A anormalidade da função hepática é comum em pacientes que são admitidos nas unidades de tratamento intensivo e sua presença é um indicador de desfecho de curto prazo ruim.

Indocyanine green clearance test as a predictor of chemotherapy liver toxicity and post-operative complications in patients with colorectal liver metastases.

OBJECTIVE: This study aims to investigate the relationship between the pre-operative indocyanine green (ICG) test, the chemotherapy-associated liver injury (CALI), and the development of severe post-operative complications (POC) in patients operated of colorectal liver metastases (CRLMs). MATERIALS AND METHODS: Sixty-nine patients previously treated with chemotherapy and submitted to liver resection for CRLM were retrospectively studied. Two pathologists independently reviewed the pathological specimens and assessed the presence of CALI. The correlation between ICG clearance and specific pathological features was analyzed. In addition, a logistic regression analysis was performed to seek for pre-operative factors associated with severe complications. RESULTS: After a mean of 10.6 (± 7.5) chemotherapy cycles, 44 patients (63.8%) developed CALI. ICG retention rate at 15 min (ICG-R15) was not statistically different between patients with and without CALI and it could only discriminate the presence of centrilobular fibrosis. Rate of severe complications was almost 6-fold in patients with CALI compared to patients without CALI (p = 0.024). ICG-R15 ≥ 10% was the only independent risk factor associated with severe POC at multivariable logistic regression (OR = 4.075 95% CI: 1.077-15.422, p = 0.039). CONCLUSIONS: Pre-operative ICG clearance test, although not useful to identify patients with hepatic drug toxicity, is a strong predictor for the development of severe post-hepatectomy complications.

OBJETIVO: Investigar la relación entre el test de aclaramiento del verde de indocianina (ICG) preoperatorio, las alteraciones patológicas derivadas de la quimioterapia (CALI) y el desarrollo de complicaciones posoperatorias en los pacientes sometidos a resección hepática por metástasis de cáncer colorrectal (MCCR). MATERIAL Y MÉTODOS: Sesenta y nueve pacientes previamente tratados con quimioterapia y operados de MCCR se estudiaron de manera retrospectiva. Dos patólogas revisaron independientemente el parénquima hepático no tumoral de los especímenes y determinaron la presencia de daño quimio-inducido. Se analizó la correlación entre el aclaramiento de ICG y las diferentes alteraciones anatomo-patológicas encontradas. Además, se realizó un análisis de regresión logística para identificar los factores preoperatorios asociados con las complicaciones posoperatorias. RESULTADOS: Tras una media de 10.6 (± 7.5) ciclos de quimioterapia, 44 pacientes (63.8%) desarrollaron CALI. La tasa de retención de ICG a los 15 minutos (ICG-R15) no fue estadísticamente diferente entre los pacientes con y sin CALI y solo pudo discriminar la presencia de fibrosis centrolobulillar. La tasa de complicaciones severas posoperatorias fue 6 veces superior en los pacientes con CALI, comparada con aquella de los pacientes sin CALI (p = 0.024). Un ICG-R15 ≥ 10% fue el único factor de riesgo independiente asociado a complicaciones severas (OR = 4.075 95% CI: 1.077-15.422, p = 0.039). CONCLUSIONES: La prueba preoperatoria de aclaramiento del ICG, a pesar de no identificar eficazmente los pacientes con daño por quimioterapia, es un fuerte predictor de desarrollo de complicaciones severas posoperatorias.

Postoperative liver function tests can predict anastomotic dysfunction after bile duct injury repair.

Liver function tests help in the follow-up of postoperative patients with iatrogenic bile duct injury. There is not clear evidence regarding their predictive role on anastomosis dysfunction. We describe our experience with postoperative liver function tests and a predictive model of long-term patency after repair. This is retrospective cohort study of patients with bilioenteric anastomosis for bile duct injury and their long-term follow-up. A binomial logistic regression model was performed to ascertain the effects of the grade of bile duct injury and liver function test in the postoperative period. A total of 329 patients were considered for the analysis. In the logistic regression model two predictor variables were statistically significant for anastomosis stenosis: type of bilioenteric anastomosis and alkaline phosphatase levels. A ROC curve analysis was made for alkaline phosphatase with an area under the curve of 0.758 (95% CI 0.67-0.84). A threshold of 323 mg/dL was established (OR 6.0, 95% CI 2.60-13.83) with a sensitivity of 75%, specificity of 67%, PPV of 20%, NPV of 96%, PLR of 2.27 and NLR of 0.37. Increased alkaline phosphatase (above 323 mg/dL) after the fourth operative week was found to be a predictor of long-term dysfunction.

Liver cirrhosis is a risk factor for poor prognosis of acute cholangitis caused by choledocholithiasis.

INTRODUCTION AND OBJECTIVES: Acute cholangitis, which is characterized by biliary infection and acute liver injury, may impact cirrhosis prognosis. However, the prognosis itself remains unclear. MATERIALS AND METHODS: This multicenter retrospective cohort study compared the mortality and liver function change between patients with and without cirrhosis who underwent endoscopic treatment for acute cholangitis caused by choledocholithiasis between January 2004 and December 2019. RESULTS: We analyzed 699 patients, 44 of whom had cirrhosis. The cirrhotic group had a significantly higher 30-day mortality rate than the noncirrhotic group (14% vs. 1%; P < 0.001). The cirrhotic group also had significantly lower total bilirubin and albumin recovery. However, all patients with cirrhosis who survived achieved total-bilirubin recovery, and 91% achieved albumin recovery within 90 days. In multivariable Cox regression analysis, the independent risk factors for total-bilirubin recovery included cirrhosis (hazard ratio, 0.37; 95%CI, 0.24‒0.58; P < 0.001) and high total-bilirubin level (0.46; 95%CI, 0.34‒0.60; P < 0.001), whereas those for albumin recovery were cirrhosis (0.51; 95%CI, 0.33‒0.79; P = 0.002), high age (0.62; 95%CI, 0.47‒0.82; P < 0.001), organ dysfunction (0.62; 95%CI, 0.39‒0.96; P = 0.03), low albumin level (0.57; 95%CI, 0.36‒0.91; P = 0.02), and high C-reactive protein level (0.73; 95%CI, 0.56‒0.95; P = 0.02). CONCLUSIONS: Patients with cirrhosis complicated with acute cholangitis had poor prognosis. Recovery of liver function after endoscopic treatment was slow; nevertheless, most patients who survived could recover within 90 days.